Development of novel therapeutic strategy targeting CML stem cells through STAT-C/EBPbeta pathway

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kyoto University
• Principal Investigator: Yokota Asumi 京都大学, 医学(系)研究科(研究院), 研究員 (00571556)
• Co-Investigator(Kenkyū-buntansha): HIRAI Hideyo 京都大学, 医学研究科, 助教 (50315933)
• Co-Investigator(Renkei-kenkyūsha): MAEKAWA Taira 京都大学, 医学研究科, 教授 (80229286)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 転写因子 / 慢性骨髄性白血病

Outline of Final Research Achievements

By analysis using a next-generation sequencer, we identified a novel 3’ distal enhancer region of Cebpb, where STAT5 are recruited in a BCR-ABL signaling-dependent manner.
We also found that IFNα, which has been used for the treatment of CML, can efficiently upregulate C/EBPβ expression, and promote exhaustion and differentiation of CML stem cells through C/EBPβ. Interestingly, IFNα phosphorylate STAT5 including STAT1 and STAT3, and recruited STAT5 to a Cebpb enhancer region, which we identified in this study. IFNα also decreased CML stem cells in a mouse model, and this effect is abolished in C/EBPβ-deficient CML stem cells, indicating that the in vivo effect of IFNα is mediated by C/EBPβ.

Free Research Field

腫瘍学